RESUMO
Although intergenic long noncoding RNAs (lincRNAs) have been linked to gene regulation in various tissues, little is known about lincRNA transcriptomes in the T cell lineages. Here we identified 1,524 lincRNA clusters in 42 T cell samples, from early T cell progenitors to terminally differentiated helper T cell subsets. Our analysis revealed highly dynamic and cell-specific expression patterns for lincRNAs during T cell differentiation. These lincRNAs were located in genomic regions enriched for genes that encode proteins with immunoregulatory functions. Many were bound and regulated by the key transcription factors T-bet, GATA-3, STAT4 and STAT6. We found that the lincRNA LincR-Ccr2-5'AS, together with GATA-3, was an essential component of a regulatory circuit in gene expression specific to the TH2 subset of helper T cells and was important for the migration of TH2 cells.
Assuntos
Regulação da Expressão Gênica/imunologia , Células Precursoras de Linfócitos T/metabolismo , RNA Longo não Codificante/genética , Células Th1/metabolismo , Células Th17/metabolismo , Células Th2/metabolismo , Animais , Diferenciação Celular , Movimento Celular , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/imunologia , Fator de Transcrição GATA3/metabolismo , Loci Gênicos , Camundongos , Camundongos Endogâmicos C57BL , Anotação de Sequência Molecular , Células Precursoras de Linfócitos T/citologia , Células Precursoras de Linfócitos T/imunologia , Ligação Proteica , RNA Longo não Codificante/imunologia , Fator de Transcrição STAT4/genética , Fator de Transcrição STAT4/imunologia , Fator de Transcrição STAT4/metabolismo , Fator de Transcrição STAT6/genética , Fator de Transcrição STAT6/imunologia , Fator de Transcrição STAT6/metabolismo , Transdução de Sinais , Proteínas com Domínio T/genética , Proteínas com Domínio T/imunologia , Proteínas com Domínio T/metabolismo , Células Th1/citologia , Células Th1/imunologia , Células Th17/citologia , Células Th17/imunologia , Células Th2/citologia , Células Th2/imunologia , Transcriptoma/imunologiaRESUMO
The spatial folding of eukaryotic genome plays a key role in genome function. We report here that our recently developed method, Hi-TrAC, which specializes in detecting chromatin loops among accessible genomic regions, can detect active sub-TADs with a median size of 100 kb, most of which harbor one or two cell specifically expressed genes and regulatory elements such as super-enhancers organized into nested interaction domains. These active sub-TADs are characterized by highly enriched histone mark H3K4me1 and chromatin-binding proteins, including Cohesin complex. Deletion of selected sub-TAD boundaries have different impacts, such as decreased chromatin interaction and gene expression within the sub-TADs or compromised insulation between the sub-TADs, depending on the specific chromatin environment. We show that knocking down core subunit of the Cohesin complex using shRNAs in human cells or decreasing the H3K4me1 modification by deleting the H3K4 methyltransferase Mll4 gene in mouse Th17 cells disrupted the sub-TADs structure. Our data also suggest that super-enhancers exist as an equilibrium globule structure, while inaccessible chromatin regions exist as a fractal globule structure. In summary, Hi-TrAC serves as a highly sensitive and inexpensive approach to study dynamic changes of active sub-TADs, providing more explicit insights into delicate genome structures and functions.
Assuntos
Cromatina , Elementos Facilitadores Genéticos , Técnicas Genéticas , Sequências Reguladoras de Ácido Nucleico , Animais , Humanos , Camundongos , Montagem e Desmontagem da Cromatina , GenomaRESUMO
Nucleosome positioning is critical to chromatin accessibility and is associated with gene expression programs in cells1-3. Previous nucleosome mapping methods assemble profiles from cell populations and reveal a cell-averaged pattern: nucleosomes are positioned and form a phased array that surrounds the transcription start sites of active genes3-6 and DNase I hypersensitive sites7. However, even in a homogenous population of cells, cells exhibit heterogeneity in expression in response to active signalling8,9 that may be related to heterogeneity in chromatin accessibility10-12. Here we report a technique, termed single-cell micrococcal nuclease sequencing (scMNase-seq), that can be used to simultaneously measure genome-wide nucleosome positioning and chromatin accessibility in single cells. Application of scMNase-seq to NIH3T3 cells, mouse primary naive CD4 T cells and mouse embryonic stem cells reveals two principles of nucleosome organization: first, nucleosomes in heterochromatin regions, or that surround the transcription start sites of silent genes, show large variation in positioning across different cells but are highly uniformly spaced along the nucleosome array; and second, nucleosomes that surround the transcription start sites of active genes and DNase I hypersensitive sites show little variation in positioning across different cells but are relatively heterogeneously spaced along the nucleosome array. We found a bimodal distribution of nucleosome spacing at DNase I hypersensitive sites, which corresponds to inaccessible and accessible states and is associated with nucleosome variation and variation in accessibility across cells. Nucleosome variation is smaller within single cells than across cells, and smaller within the same cell type than across cell types. A large fraction of naive CD4 T cells and mouse embryonic stem cells shows depleted nucleosome occupancy at the de novo enhancers detected in their respective differentiated lineages, revealing the existence of cells primed for differentiation to specific lineages in undifferentiated cell populations.
Assuntos
Eucromatina/metabolismo , Inativação Gênica , Heterocromatina/metabolismo , Nuclease do Micrococo/metabolismo , Nucleossomos/genética , Nucleossomos/metabolismo , Análise de Célula Única , Células 3T3 , Animais , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular/genética , Linhagem da Célula/genética , Células Cultivadas , Desoxirribonuclease I/metabolismo , Elementos Facilitadores Genéticos/genética , Eucromatina/genética , Genoma/genética , Heterocromatina/genética , Masculino , Camundongos , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Especificidade de Órgãos/genética , Sítio de Iniciação de TranscriçãoRESUMO
Change history: In Fig. 1c of this Letter, the two graphs were duplicates. The right panel of Fig. 1c has been corrected online.
RESUMO
Investigating chromatin interactions between regulatory regions such as enhancer and promoter elements is vital for understanding the regulation of gene expression. Compared to Hi-C and its variants, the emerging 3D mapping technologies focusing on enriched signals, such as TrAC-looping, reduce the sequencing cost and provide higher interaction resolution for cis-regulatory elements. A robust pipeline is needed for the comprehensive interpretation of these data, especially for loop-centric analysis. Therefore, we have developed a new versatile tool named cLoops2 for the full-stack analysis of these 3D chromatin interaction data. cLoops2 consists of core modules for peak-calling, loop-calling, differentially enriched loops calling and loops annotation. It also contains multiple modules for interaction resolution estimation, data similarity estimation, features quantification, feature aggregation analysis, and visualization. cLoops2 with documentation and example data are open source and freely available at GitHub: https://github.com/KejiZhaoLab/cLoops2.
Assuntos
Montagem e Desmontagem da Cromatina , Cromatina/química , Software , Linhagem Celular Tumoral , Cromatina/genética , Cromatina/metabolismo , Biologia Computacional/métodos , HumanosRESUMO
A new compact tandem excitation source was designed and constructed by using an array point discharge (ArrPD) microplasma for a miniaturized optical emission spectrometer through coupling a hydride generation (HG) unit as a sample introduction device. Three pairs of point discharges were arranged in sequence in a narrow discharge chamber to construct the ArrPD microplasma, for improved excitation capability owing to the serial excitation. Besides, the discharge plasma region was greatly enlarged, therefore, more gaseous analytes could be intercepted to enter into the microplasma for sufficient excitation, for improved excitation efficiency and OES signal. To better understand the effectiveness of the proposed ArrPD source, a new instrument for simultaneous detection of atomic emission and absorption spectral responses was also proposed, designed, and constructed to reveal the excitation and enhancement process in the discharge chamber. Under the optimized conditions, the limits of detection (LODs) of As, Ge, Hg, Pb, Sb, Se, and Sn were 0.7, 0.4, 0.05, 0.7, 0.3, 2, and 0.08 µg L-1, respectively, and the relative standard deviations (RSDs) were all less than 4%. Compared with a commonly used single point discharge microplasma source, the analytical sensitivities of these seven elements were improved by 3-6-fold. Certified Reference Materials (CRMs) were successfully analyzed with this miniaturized spectrometer, which features low power, compactness, portability, and high detectability, and is thereby a great prospect in the field of elemental analytical chemistry.
RESUMO
In this work, a simple and novel method coupling solid phase extraction (SPE) with X-ray fluorescence spectrometry (XRF) is proposed for the simultaneous determination of 15 kinds of trace rare earth elements (REEs) in water samples. A phosphonic acid functionalized metal-organic framework named BPG-MIL-53(Al) was prepared via postsynthetic modification and served as an efficient adsorbent for these REEs. The prepared BPG-MIL-53(Al) could almost completely adsorb REEs in 5 min under neutral conditions. After filtration, REEs-adsorbed BPG-MIL-53(Al) was deposited on a filter membrane to form a thin film, which was directly analyzed by XRF. The XRF intensities of the REEs-retained MOF disc remained almost unchanged after six months. Taking advantage of this strategy, XRF was able to quantitate ng mL-1 levels of REEs in water samples, achieving impressive limits of detection in the range of 0.4-4.7 ng mL-1. The proposed method was applied to the on-site collection and analysis of REEs in real water samples with desirable accuracy and spike recoveries obtained.
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This study was conducted to evaluate the effects of a low-protein (LP) diet supplemented with sodium butyrate (SB), medium-chain fatty acids (MCFAs) and n-3 polyunsaturated fatty acids (PUFAs) on nutrient utilization and lipid and amino acid metabolism in weaned pigs. A total of 120 Duroc × Landrace × Yorkshire pigs (initial body weight: 7.93 ± 0.65 kg) were randomly assigned to five dietary treatments, including the control diet (CON), LP diet, LP + 0.2% SB diet (LP + SB), LP + 0.2% MCFA diet (LP + MCFA) and LP + 0.2% n-3 PUFA diet (LP + PUFA). The results show that the LP + MCFA diet increased (p < 0.05) the digestibility of dry matter and total P in pigs compared with the CON and LP diets. In the liver of the pigs, the metabolites involved in sugar metabolism and oxidative phosphorylation significantly changed with the LP diet compared with the CON diet. Compared with the LP diet, the altered metabolites in the liver of the pigs fed with the LP + SB diet were mainly associated with sugar metabolism and pyrimidine metabolism; the altered metabolites in the liver of pigs fed with the LP + MCFA and LP + PUFA diets were mainly associated with lipid metabolism and amino acid metabolism. In addition, the LP + PUFA diet increased (p < 0.05) the concentration of glutamate dehydrogenase in the liver of pigs compared with the LP diet. Furthermore, the LP + MCFA and LP + PUFA diets increased (p < 0.05) the mRNA abundance of sterol regulatory element-binding protein 1 and acetyl-CoA carboxylase in the liver compared with the CON diet. The LP + PUFA diet increased (p < 0.05) mRNA abundances of fatty acid synthase in the liver compared with the CON and LP diets. Collectively, the LP diet supplemented with MCFAs improved nutrient digestibility, and the LP diet supplemented with MCFAs and n-3 PUFAs promoted lipid and amino acid metabolisms.
Assuntos
Ácidos Graxos Ômega-3 , Ácidos Graxos , Suínos , Animais , Ácidos Graxos/farmacologia , Dieta com Restrição de Proteínas , Suplementos Nutricionais , Dieta , Nutrientes , Ácidos Graxos Insaturados , Ácido Butírico , Aminoácidos/metabolismo , Açúcares , Ração Animal/análiseRESUMO
This study aimed to investigate the effects of low-protein (LP) diets supplemented with sodium butyrate (SB), medium-chain fatty acids (MCT), or n-3 polyunsaturated fatty acids (n-3 PUFA) on the growth performance, immune function, and the microbiome of weaned piglets. A total of 120 healthy weaned piglets ((Landrace × Large White × Duroc); 7.93 ± 0.7 kg initial body weight), were randomly divided into five groups. Each group consisted of six replications with four piglets per replication. Dietary treatments included control diet (CON); LP diet (LP); LP + 0.2% SB diet (LP + SB); LP + 0.2% MCT diet (LP + MCT); and LP + PUFA diet (LP + PUFA). The experimental period lasted for 4 weeks. Compared with the CON diet, LP, LP + SB, LP + MCT, and LP + PUFA diets decreased the final weight and average daily gain (ADG) of piglets (p < 0.05). There were lower (p < 0.05) concentrations of IL-8 and higher (p < 0.05) Glutathione peroxidase (GSH-Px) activity in the plasma of piglets fed with LP + SB, LP + MCT, and LP + PUFA diets than those fed with the LP diet. The piglets in the LP + SB and LP + PUFA groups had lower IKK-alpha (IKKa) mRNA expression in the colonic mucosa compared with those in the CON and LP groups (p < 0.05). The mRNA expression of TLR4 in the colonic mucosa of piglets in the LP + SB, LP + MCT, and LP + PUFA groups was decreased when compared with the CON and LP groups (p < 0.05). The LP + MCT diets increased the gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in the colonic mucosa of piglets compared with CON, LP, and LP + SB diets (p < 0.05). The abundance of Erysipelotrichaceae in the colonic microbiome of piglets in the LP group was higher than that in the other four groups (p < 0.05). Collectively, this study showed that LP diets supplemented with SB, MCT, or n-3 PUFA reduced plasma inflammatory factor levels, increased plasma GSH-Px activity, and declined mRNA expression of TLR4 and IKKa in the colonic epithelium, whereas it reduced the abundance of Erysipelotrichaceae in the colon of piglets.
Assuntos
Ácidos Graxos Ômega-3 , Microbiota , Animais , Suínos , Ácido Butírico , Dieta com Restrição de Proteínas , Ácidos Graxos Ômega-3/farmacologia , Receptor 4 Toll-Like/genética , Ácidos Graxos , Antioxidantes/metabolismo , RNA Mensageiro , ImunidadeRESUMO
Our method for analyzing histone modifications, scChIC-seq (single-cell chromatin immunocleavage sequencing), involves targeting of the micrococcal nuclease (MNase) to a histone mark of choice by tethering to a specific antibody. Cleaved target sites are then selectively PCR amplified. We show that scChIC-seq reliably detects H3K4me3 and H3K27me3 target sites in single human white blood cells. The resulting data are used for clustering of blood cell types.
Assuntos
Cromatina/química , Histonas/química , Nuclease do Micrococo/química , Animais , Anticorpos/química , Imunoprecipitação da Cromatina , Biologia Computacional , DNA/química , Epigenômica , Genoma , Sequenciamento de Nucleotídeos em Larga Escala , Código das Histonas , Humanos , Leucócitos/citologia , Leucócitos/metabolismo , Masculino , Camundongos , Células NIH 3T3 , Nucleossomos , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Processamento de Proteína Pós-Traducional , Reprodutibilidade dos Testes , Análise de Sequência de DNA , SoftwareRESUMO
The histone variant H3.3 is deposited across active genes, regulatory regions, and telomeres. It remains unclear how H3.3 interacts with chromatin modifying enzymes and thereby modulates gene activity. In this study, we performed a co-immunoprecipitation-mass spectrometry analysis of proteins associated with H3.3-containing nucleosomes and identified the nucleosome remodeling and deacetylase complex (NuRD) as a major H3.3-interactor. We show that the H3.3-NuRD interaction is dependent on the H3.3 lysine 4 residue and that NuRD binding occurs when lysine 4 is in its unmodified state. The majority of NuRD binding colocalizes with H3.3 and directly correlates with gene activity. H3.3 depletion led to reduced levels of NuRD at sites previously occupied by H3.3, as well as a global decrease in histone marks associated with gene activation. Our results demonstrate the importance of H3.3 in the maintenance of the cellular epigenetic landscape and reveal a highly prevalent interaction between the histone variant H3.3 and the multiprotein complex NuRD.
Assuntos
Código das Histonas , Histonas/metabolismo , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/metabolismo , Células 3T3 , Animais , Sítios de Ligação , Epigênese Genética , Histonas/química , Histonas/genética , Camundongos , Ligação ProteicaRESUMO
Long-range chromatin interactions play critical roles in genome organization and regulation of transcription. We now report transposase-mediated analysis of chromatin looping (Trac-looping) for simultaneous detection of multiscale genome-wide chromatin interactions among regulatory elements and chromatin accessibility. With this technique, a bivalent oligonucleotide linker is inserted between two interacting regions such that the chromatin interactions are captured without prior chromatin fragmentation and proximity-based ligation. Application of Trac-looping to human CD4+ T cells revealed substantial reorganization of enhancer-promoter interactions associated with changes in gene expression after T cell receptor stimulation.
Assuntos
Cromatina/metabolismo , Genoma Humano , Cromatina/química , Biologia Computacional , Elementos Facilitadores Genéticos , Humanos , Regiões Promotoras Genéticas , Transcrição GênicaRESUMO
DNase I hypersensitive sites (DHSs) provide important information on the presence of transcriptional regulatory elements and the state of chromatin in mammalian cells. Conventional DNase sequencing (DNase-seq) for genome-wide DHSs profiling is limited by the requirement of millions of cells. Here we report an ultrasensitive strategy, called single-cell DNase sequencing (scDNase-seq) for detection of genome-wide DHSs in single cells. We show that DHS patterns at the single-cell level are highly reproducible among individual cells. Among different single cells, highly expressed gene promoters and enhancers associated with multiple active histone modifications display constitutive DHS whereas chromatin regions with fewer histone modifications exhibit high variation of DHS. Furthermore, the single-cell DHSs predict enhancers that regulate cell-specific gene expression programs and the cell-to-cell variations of DHS are predictive of gene expression. Finally, we apply scDNase-seq to pools of tumour cells and pools of normal cells, dissected from formalin-fixed paraffin-embedded tissue slides from patients with thyroid cancer, and detect thousands of tumour-specific DHSs. Many of these DHSs are associated with promoters and enhancers critically involved in cancer development. Analysis of the DHS sequences uncovers one mutation (chr18: 52417839G>C) in the tumour cells of a patient with follicular thyroid carcinoma, which affects the binding of the tumour suppressor protein p53 and correlates with decreased expression of its target gene TXNL1. In conclusion, scDNase-seq can reliably detect DHSs in single cells, greatly extending the range of applications of DHS analysis both for basic and for translational research, and may provide critical information for personalized medicine.
Assuntos
Cromatina/genética , Cromatina/metabolismo , Desoxirribonuclease I/metabolismo , Formaldeído , Genoma/genética , Inclusão em Parafina , Análise de Célula Única/métodos , Fixação de Tecidos , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/patologia , Animais , Elementos Facilitadores Genéticos/genética , Perfilação da Expressão Gênica , Histonas/metabolismo , Humanos , Camundongos , Mutação/genética , Células NIH 3T3 , Regiões Promotoras Genéticas/genética , Reprodutibilidade dos Testes , Tiorredoxinas/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Proteína Supressora de Tumor p53/metabolismoRESUMO
The transcription factor GATA3 plays an essential role during T cell development and T helper 2 (Th2) cell differentiation. To understand GATA3-mediated gene regulation, we identified genome-wide GATA3 binding sites in ten well-defined developmental and effector T lymphocyte lineages. In the thymus, GATA3 directly regulated many critical factors, including Th-POK, Notch1, and T cell receptor subunits. In the periphery, GATA3 induced a large number of Th2 cell-specific as well as Th2 cell-nonspecific genes, including several transcription factors. Our data also indicate that GATA3 regulates both active and repressive histone modifications of many target genes at their regulatory elements near GATA3 binding sites. Overall, although GATA3 binding exhibited both shared and cell-specific patterns among various T cell lineages, many genes were either positively or negatively regulated by GATA3 in a cell type-specific manner, suggesting that GATA3-mediated gene regulation depends strongly on cofactors existing in different T cells.
Assuntos
Fator de Transcrição GATA3/metabolismo , Proteínas Mutantes/metabolismo , Subpopulações de Linfócitos T/metabolismo , Células Th2/metabolismo , Animais , Linhagem da Célula/genética , Metilação de DNA , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/imunologia , Regulação da Expressão Gênica , Genoma/imunologia , Estudo de Associação Genômica Ampla , Histonas/genética , Histonas/metabolismo , Linfopoese/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Mutantes/genética , Proteínas Mutantes/imunologia , Ligação Proteica , Receptor Notch1/genética , Receptor Notch1/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologia , Células Th2/imunologia , Células Th2/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Enhancers of transcription activate transcription via binding of sequence-specific transcription factors to their target sites in chromatin. In this report, we identify GATA1-bound distal sites genome-wide and find a global reorganization of the nucleosomes at these potential enhancers during differentiation of hematopoietic stem cells (HSCs) to erythrocytes. We show that the catalytic subunit BRG1 of BAF complexes localizes to these distal sites during differentiation and generates a longer nucleosome linker region surrounding the GATA1 sites by shifting the flanking nucleosomes away. Intriguingly, we find that the nucleosome shifting specifically facilitates binding of TAL1 but not GATA1 and is linked to subsequent transcriptional regulation of target genes.
Assuntos
DNA Helicases/metabolismo , Elementos Facilitadores Genéticos , Fator de Transcrição GATA1/metabolismo , Regulação da Expressão Gênica , Proteínas Nucleares/metabolismo , Nucleossomos , Fatores de Transcrição/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Sítios de Ligação , Fator de Ligação a CCCTC , Diferenciação Celular/genética , Células Cultivadas , Montagem e Desmontagem da Cromatina , Imunoprecipitação da Cromatina , DNA Helicases/genética , Hematopoese/genética , Células-Tronco Hematopoéticas/fisiologia , Humanos , Proteínas Nucleares/genética , Especificidade de Órgãos , Cultura Primária de Células , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/metabolismo , Proteína 1 de Leucemia Linfocítica Aguda de Células T , Fatores de Transcrição/genética , Transcrição GênicaRESUMO
BACKGROUND: Trigger thumb is a prevalent hand condition observed in children, and its management remains a topic of considerable debate, ranging from mere observation to surgical intervention. In recent times, there has been a growing interest in exploring nonoperative treatments as alternatives to surgical procedures for managing pediatric trigger thumb. Gaining insight into the prevalence of spontaneous resolution in pediatric trigger thumb is of paramount importance. However, the literature presents a wide variation in estimates regarding the prevalence of this spontaneous resolution, highlighting the need for further investigation and consensus. The aim of this review was to estimate the overall prevalence of spontaneous resolution among pediatric trigger thumb. METHODS: This study meticulously followed the PRISMA guidelines and registered in the PROSPERO. The PubMed, Embase, and Cochrane Library databases were searched for all relevant studies up to May 2024.Inclusion criteria were studies reported only observation spontaneous resolution pediatric trigger thumb, aged up to 14 years, reported at least 10 thumbs and followed up time at least 3 months. Confounded intervention treatment measure studies were excluded. To synthesize the prevalence rates from individual studies, we employed a random-effects meta-analysis. In order to uncover the sources of heterogeneity and to compare prevalence estimates across different groups, we performed sensitivity and subgroup analyses. To meticulously evaluate the quality of the included studies, the Joanna Briggs Institute's quality assessment checklist was employed. Furthermore, to assess the heterogeneity among the studies, both Cochran's Q test and the I² statistic were utilized. RESULTS: A total of eleven studies were included for the final analysis, with 599 pediatric trigger thumbs. Our final meta-analysis showed that more than one-third of these pediatric trigger thumb cases resolved spontaneously, with a resolution rate of 43.5% (95% CI 29.6-58.6). Subgroup analyses showed that in terms of age at the first visit, the prevalence of spontaneous resolution in the less than 24 months group and in the 24 months or older group was 38.7%(95% CI 18.1-64.4)and 45.8%(95% CI 27.4-65.4), respectively. There was no significant difference between the two groups(P = 0.690). When analyzing follow up time, the prevalence of spontaneous resolution in the 24 months or longer group and in the less than 24 months group was 58.9%(95% CI 41.6-74.2)and 26.8%(95% CI 14.7-43.8), respectively.There was significant statistical differences between the two groups(P = 0.009). Based on the initial severity of interphalangeal (IP) joint flexion contracture, the prevalence of spontaneous resolution in the 30 degrees or less group and in the other measurements group was 54.1%(95% CI 31.5-75.1)and 37.1%(95% CI 21.9-55.4), respectively.There was no significant difference between the two groups(P = 0.259). CONCLUSION: Our study demonstrates that a significant proportion of pediatric trigger thumbs resolve spontaneously. This finding highlights the benefits of early observation in managing this condition. By prioritizing non-operative observation, both parents and surgeons are better equipped to make informed decisions regarding the treatment of pediatric trigger thumb, potentially reducing the need for surgical intervention.
Assuntos
Remissão Espontânea , Dedo em Gatilho , Humanos , Dedo em Gatilho/epidemiologia , Criança , Prevalência , Adolescente , Pré-Escolar , Feminino , Masculino , LactenteRESUMO
Nanoparticle-mediated drug delivery has emerged as a highly promising and effective therapeutic approach for addressing myocardial infarction. However, clinical translation tends to be a failure due to low cardiac retention as well as liver and spleen entrapment in previous therapies. Herein, we report a two-step exosome delivery system, which precludes internalization by the mononuclear phagocyte system before the delivery of therapeutic cardiac targeting exosomes (ExoCTP). Importantly, curcumin released by ExoCTP diminishes reactive oxygen species over-accumulation in ischemic myocardium, as well as serum levels of lactate dehydrogenase, malonyldialdehyde, superoxide dismutase and glutathione, indicating better antioxidant capacity than free curcumin. Finally, our strategy was proven to greatly potentiate the delivery and therapeutic efficacy of curcumin without systemic toxicity. Taken together, our smart exosome-mediated drug delivery strategy can serve either as therapeutics alone or in combination with other drugs for effective heart targeting and subsequent wound healing.
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Infarct healing requires a dynamic and orchestrated inflammatory reaction following myocardial infarction (MI). While an uncontrolled excessive inflammatory response exaggerates ischemic injury post-MI, M2-like reparative macrophages may facilitate inflammation regression and promote myocardial healing. However, how protein post-translational modification regulates post-MI cardiac repair and dynamic myeloid activation remains unknown. Here we show that M2-like reparative, but not M1-like inflammatory activation, is enhanced by pharmacologically-induced hyper-O-GlcNAcylation. Mechanistically, myeloid knockdown of O-GlcNAc hydrolase O-GlcNAcase (Oga), which also results in hyper-O-GlcNAcylation, positively regulates M2-like activation in a STAT6-dependent fashion, which is controlled by O-GlcNAcylation of STAT6. Of note, both systemic and local supplementation of thiamet-G (TMG), an Oga inhibitor, effectively facilitates cardiac recovery in mice by elevating the accumulation of M2-like macrophages in infarcted hearts. Our study provides a novel clue for monocyte/macrophage modulating therapies aimed at reducing post-MI hyperinflammation in ischemic myocardium.
Assuntos
Hidrogéis , Infarto do Miocárdio , Camundongos , Animais , Hidrogéis/metabolismo , Miocárdio/metabolismo , Coração , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Processamento de Proteína Pós-Traducional , Acetilglucosaminidase/metabolismoRESUMO
Protein is the most important macro-nutrient when it comes to maximizing health, body composition, muscle growth, and recovery of body tissue. In recent years, it has been found that protein also plays an important role in metabolism and gut microbiota. This study was performed to investigate the effects of an isocaloric diet with different crude protein contents on the energy metabolism of Sprague-Dawley (SD) rats. Results revealed that compared with the 20% crude protein (CP; control) diet, the 38% CP diet improved serum parameters that are associated with dyslipidemia and glucose metabolic disorders in SD rats, whereas the 50% CP diet increased liver injury indicators and fatty acid synthesis-related genes and protein expression in the liver. Compared with the control diet, the 14% CP diet increased the abundance of colonic short-chain fatty acid-producing bacteria (Lachnospiraceae_NK4A136_group and Ruminiclostridium_9) and promoted colonic microbial cysteine and methionine metabolism, the 38% CP diet up-regulated colonic microbial lysine biosynthesis and degradation pathways, and the 50% CP diet down-regulated colonic mucosal cholesterol metabolism. Furthermore, the increase of multiple colonic enteropathogenic bacteria in the 50% CP group was associated with higher palmitic acid and stearic acid concentrations in the colonic microbes and lower cholesterol and arachidonic acid concentrations in the colonic mucosa. These findings revealed that the 14% CP and 38% CP diets improved rats' energy metabolism, while the 50% CP diet was accompanied by lipid metabolism imbalances and an increase in the abundance of multiple enteropathogenic bacteria.
Assuntos
Microbioma Gastrointestinal , Ratos , Animais , Ratos Sprague-Dawley , Dieta , Ácidos Graxos Voláteis/farmacologia , Colesterol/farmacologia , Metabolismo Energético , Metabolismo dos LipídeosRESUMO
Post-weaning diarrhea (PWD) is a globally significant threat to the swine industry. Historically, antibiotics as well as high doses of zinc oxide and copper sulfate have been commonly used to control PWD. However, the development of bacterial resistance and environmental pollution have created an interest in alternative strategies. In recent years, the research surrounding these alternative strategies and the mechanisms of piglet diarrhea has been continually updated. Mechanically, diarrhea in piglets is a result of an imbalance in intestinal fluid and electrolyte absorption and secretion. In general, enterotoxigenic Escherichia coli (ETEC) and diarrheal viruses are known to cause an imbalance in the absorption and secretion of intestinal fluids and electrolytes in piglets, resulting in diarrhea when Cl- secretion-driven fluid secretion surpasses absorptive capacity. From a perspective of feedstuffs, factors that contribute to imbalances in fluid absorption and secretion in the intestines of weaned piglets include high levels of crude protein (CP), stimulation by certain antigenic proteins, high acid-binding capacity (ABC), and contamination with deoxynivalenol (DON) in the diet. In response, efforts to reduce CP levels in diets, select feedstuffs with lower ABC values, and process feedstuffs using physical, chemical, and biological approaches are important strategies for alleviating PWD in piglets. Additionally, the diet supplementation with additives such as vitamins and natural products can also play a role in reducing the diarrhea incidence in weaned piglets. Here, we examine the mechanisms of absorption and secretion of intestinal fluids and electrolytes in piglets, summarize nutritional strategies to control PWD in piglets from the perspective of feeds, and provide new insights towards future research directions.